R & D – New Drug Development

Burn Wounds

Xylentra is the first synthetic peptide based topical product useful in burn wound care. All the three phases of clinical development have been completed in India and a dossier has been submitted to the Indian Regulatory for marketing approval. In the Phase III Clinical trial, apart from controlling infection, fastened wound healing, the product improved quality of life in burn wound patients, by reducing Post-Burn effects.

The Phase III Clinical Trial data has been presented at 17th Congress of the International Society for Burn Injuries (ISBI) on 14th October 2014 in Sydney, Australia.

A burn is an injury to the skin or other organic tissue primarily caused by heat or due to radiation, friction, radioactivity, electricity and contact with chemicals. Burn injuries are the most devastating of all injuries and a major public health problem. Burns are the fourth most common type of trauma worldwide. Burns constitute a major public health problem especially in low and middle-income countries where over 95% of all burn deaths occur. Burns are a global public health problem accounting for an estimated 3,00,000 deaths annually. In India, over 1,00,000 people are moderately or severely burnt every year. Burns are one of the most common household injuries, especially among children.

Burns are characterized by severe skin damage that causes the affected skin cells to die. Burns can be classified into first, second, third and fourth degree burns. Each degree is based on the severity of damage to the skin, with first degree being the most minor and fourth degree being more severe.

The most minor and third-degree being the most severe. Damage includes:

First-degree burns: Affects only epidermis. The burn site is red and no blisters can be seen on the skin.

Second-degree burns: Involves the epidermis and part of the dermis layer. The burn site is red with blistered skin which may be swollen and painful.

Third-degree burns: Destroys the epidermis, dermis and may go into the subcutaneous tissue. The burn site appears white and charred.

There are also fourth-degree burns: This type of burns can damage the underlying bones, muscles and tendons. Since the nerve endings are destroyed there won’t be any sensation in the area of the burn.

Burns are a leading cause of disability and disfigurement. It is estimated that fire related burns account for 10 million disability adjusted life years (DALYs) lost globally each year. Most people can recover from burns without serious health consequences, depending on the cause and degree of injury. More serious burns require immediate emergency medical care to prevent complications and death.

Most patients sustain burns of such limited severity and extent (>80% of burns involve <20% of the body surface) that they can be treated on an outpatient basis. Burn wound infection is a major cause of morbidity and mortality after initial period of shock estimating about 75% of the mortality following burn injuries is related to infections. Infection is the most common cause of morbidity and mortality in burn patients. Burn wound infection is problematic because it delays healing, encourages scarring and may result in bacteraemia, sepsis or multiple-organ dysfunction syndrome whereby organs from several systems are unable to maintain homeostasis on their own, requiring immediate medical attention. The spectrum of infection ranges from asymptomatic colonization to bacteraemia to death. Over the past 20 years, significant changes in the microbial ecology of the burn wound have been noted.

Inflammatory Bowel Disease

The Issar pharmaceuticals developed a synthetic peptide having anti-inflammatory properties studied initially by using IL-10 knock-out Murine Colitis Model and later confirmed by DSS induced rat model which was evaluated by DAI, Histopathology and Biochemical markers. After reviewing the efficacy results the proof of concept studies and toxicological studies are planned.

Ulcerative colitis (UC) is a chronic disease in which the lining of the large intestine becomes inflamed due to recurrent inflammation and the large intestine will then develop ulcers that produce pus, blood and mucus. Ulcerative colitis is one of the two major types of inflammatory bowel disease (IBD), along with Crohn disease. Crohns disease can affect any part of the gastrointestinal (GI) tract unlike Ulcerative colitis.

Ulcerative colitis (UC) has two incidence peaks, one in adolescents and young adults and the other in middle-aged men and women. Men and women are about equally affected. The exact cause of Ulcerative colitis is not known but many researchers believe that Ulcerative colitis is caused by a combination of factors that involve genetics, the environment and an overactive immune system.

Solid Cancer Tumours

The Issar developed a synthetic peptide in an injectable form, which was evaluated in a Solid Tumour Cancer Phase 1 Clinical Trial, conducted in India. The Phase I Clinical Trial data has been presented at the American Association for Cancer Research (AACR) Annual Meet 2013 held in Washington, USA.

Phase II Clinical Trial dossier has been submitted to the Indian Regulator for approval.

Dosage Form

Injectable Peptide

Clinical Trials

Phase I conducted in India.
Phase II dossier submitted to Indian Regulatory.

A tumour refers to any abnormal growth of cells and can be harmless or dangerous. Solid tumours may be benign and harmless and do not cancerous cells, or malignant and dangerous and contain cancerous cells. Solid tumours further divided into many types based on the cell types that are involved; Sarcomas, Carcinomas and Lymphomas.

Solid tumours make up about 30% of all cancers in children. The most common type of solid tumour found in children is a brain tumour. In 2005, 7.6 million people died of cancer out of 58 million deaths worldwide. More than 70% of all cancer deaths occur in low and middle-income countries, where resources available for prevention, diagnosis and treatment of cancer are limited or non-existent. Based on projections, cancer deaths will continue to rise with an estimated 11.4 million dying in 2030.

Psoriasis

Issar pharmaceuticals developed a synthetic peptide for psoriasis which has remarkable potential in efficaciously attenuating the symptoms and processes underlying psoriasis-like dermatitis in mice. The lytic synthetic peptide has an anti-angio-lytic activity and anti-inflammatory properties that could antagonize the harmful effects of the pro-inflammatory mediators responsible for the onset of the chronic disease, they may therefore prove to have potential in preventing, delaying and curing the disease and can open the way to new therapeutic strategies for psoriasis treatment.

However, though IMQ-induced dermatitis in mice may share the cytokine profile and histopathological findings to those of the psoriatic lesions in humans and further research is required to validate that they are the corresponding disease expressions. The current findings on the psoriasis-like mice model could be found appropriate on the human psoriatic model only after such validations and further clinical researches.

Another study done on the peptide has shown efficacy in multiple animal models. It inhibited various cytokines both in-vitro and in-vivo, that are implicated in psoriasis pathogenesis. The peptide is non-mutagenic, non-haemolytic. The non-GLP toxicity studies showed very good safety profile and the GLP Toxicology programme is proposed.

The peptide has completed mechanistic profiling and shown good safety profile completed acute safety studies in rodents. Safety pharmacology and long-term safety studies are proposed. The peptide has been applied for patent protection. US IND filing is planned.

The peptide has shown efficacy in multiple animal models. It inhibited various cytokines (in vitro & Invivo), that are implicated in Psoriasis pathogenesis. The peptide is non-mutagenic, non-hemolytic. Non-GLP toxicity studies showed very good safety profile. GLP Toxicology programme is proposed.

Mechanistic studies have been completed.

The peptide has been applied for patent protection. US IND filing is planned.

Psoriasis is a complex, chronic and multifactorial inflammatory skin disease, that speeds up the life cycle of the skin cells causes them to rapidly build up on the surface of the skin. Psoriasis typically occurs on knees, elbows, scalp and can affect the torso of the palm and the soles of the feet. It is non-contagious and affects all races and both sexes. The cause of the disease is unknown, but autoimmune, genetic and environmental factors are involved. Psoriasis can affect 2–4% of the worldwide population. While it affects people of all ages, disease onset is commonly between the ages of 15-25. Up to 30% of people with psoriasis will also develop psoriatic arthritis.

Diabetic Foot Ulcer

ISSAR developed a synthetic peptide that represents a giant step forward in the treatment of chronic diabetic foot ulcer. In the future, it appears hopeful that a new generation of therapy will follow synthetic peptide for the treatment these chronic wounds.

What is Diabetic foot ulcer?

Diabetic foot ulcer is a major complication of diabetes mellitus, and possibly the major constituent of the diabetic foot. It occurs in 15% of people with diabetes and precedes 84% of all diabetes-related lower-leg amputations. Diabetic neuropathic foot ulcers represent a serious health care burden to patients and to society. While the management of chronic diabetic foot ulcers has improved in recent years, it remains a frustrating problem for a variety of clinicians. Diabetes mellitus leads to a host of serious complications in multiple organ systems. Ultimately, 15%–25% of all people with diabetes will develop a foot ulcer at some point in their lifetime. The management of foot ulcers and their associated morbidities is a leading cause of hospitalizations, and the occurrence of a foot ulcer significantly increases the risk of an amputation in diabetic patients. In fact, approximately 85% of all amputations for diabetic limbs were preceded by ulcers, culminating in 60,000–80,000 amputations performed yearly secondary to the failure of such wounds to heal. Indeed, most lower extremity amputations are performed in diabetic patients. The risk of death for a diabetic person who ends up with a below-knee amputation is 50% over 5 years.